Influence of Metoclopramide on Ticagrelor Pharmacokinetics and Pharmacodynamics in Patients With Unstable Angina Pectoris on Concomitant Treatment With Morphine

March 28, 2019 updated by: Jacek Kubica, Collegium Medicum w Bydgoszczy

Differences in the Pharmacokinetic and Pharmacodynamic Profile of Ticagrelor and Its Active Metabolite AR-C124900XX Between Patients With Unstable Angina Pectoris Treated With Crushed Ticagrelor and a Combination of Morphine and Metoclopramide or Morphine Alone - a Randomized Study

The purpose of this study is to evaluate differences in the pharmacokinetics and pharmacodynamics of ticagrelor and its active metabolite between patients who received ticagrelor and morphine followed by metoclopramide versus patients treated with ticagrelor and morphine alone for unstable angina pectoris.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

According to contemporary guidelines, ticagrelor is a recommended antiplatelet agent in acute coronary syndromes, including unstable angina pectoris. Quick platelet inhibition plays pivotal role in the treatment of acute coronary syndromes. As evidenced in the IMPRESSION study, analgesia with morphine delays platelet inhibition in patients with acute myocardial infarction. On the other hand, the results of the MOJITO study prove that administration of crushed ticagrelor tablets leads to quicker platelet blockage.

Taking the above into consideration, we created a pharmacokinetic/pharmacodynamic study aiming to evaluate differences between patients who received crushed ticagrelor orally followed by either 1) a combination of intravenous morphine and metoclopramide or 2) intravenous morphine alone.

The primary study outcome is time needed for ticagrelor and its active metabolite to reach their maximum plasma concentration in each study arm. Secondary outcomes include ticagrelor and AR-C124900XX maximum concentration and the area under the plasma concentration curve for both agents.

Platelet reactivity will be assessed with the Multiplate Analyzer in all study participants at nine predefined time points.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Poland
    • Kujawsko-Pomorskie
      • Bydgoszcz, Kujawsko-Pomorskie, Poland, 85-094
        • Cardiology Department, Dr. A. Jurasz University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Provision of informed consent prior to any study specific procedures
  • Diagnosis of unstable angina
  • Male or non-pregnant female, aged 18-80 years
  • Provision of informed consent for angiography and PCI
  • GRACE score <140 pts

Exclusion Criteria:

  • treatment with ticlopidine, clopidogrel, prasugrel or ticagrelor within 14 days before the study enrollment
  • current treatment with morphine or any opioid "mi" receptor agonist
  • hypersensitivity to ticagrelor
  • current treatment with oral anticoagulant or chronic therapy with low-molecular-weight heparin
  • active bleeding
  • history of intracranial hemorrhage
  • recent gastrointestinal bleeding (within 30 days)
  • history of coagulation disorders
  • platelet count less than <100 x10^3/mcl
  • hemoglobin concentration less than 10.0 g/dl
  • history of moderate or severe hepatic impairment
  • history of major surgery or severe trauma (within 3 months)
  • risk of bradycardic events as judged by the investigator
  • second or third degree atrioventricular block during screening for eligibility
  • history of asthma or severe chronic obstructive pulmonary disease
  • kidney disease requiring dialysis
  • manifest infection or inflammatory state
  • Killip class III or IV during screening for eligibility
  • respiratory failure
  • history of severe chronic heart failure (NYHA class III or IV)
  • concomitant therapy with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir) or strong CYP3A inducers (rifampicin, phenytoin, carbamazepine, dexamethasone, phenobarbital) within 14 days and during study treatment
  • body weight below 50 kg

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Crushed ticagrelor followed by morphine
crushed ticagrelor 180 mg administered orally followed by morphine 5 mg intravenously
Drug: Crushed ticagrelor followed by morphine
Crushed ticagrelor (180 mg) followed by morphine 5 mg intravenously
Other Names:
  • Brilique
Active Comparator: Crushed ticagrelor, morphine,metoclopramide
crushed ticagrelor 180 mg administered orally followed by morphine 5 mg and metoclopramide 10 mg intravenously
Drug: Crushed ticagrelor, morphine,metoclopramide
Crushed ticagrelor (180 mg) orally followed by morphine 5 mg and metoclopramide 10 mg intravenously
Other Names:
  • Brilique

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Time to maximum concentration (tmax) for ticagrelor and AR-C124900XX for ticagrelor+morphine vs ticagrelor+morphine+metoclopramide arms
Time Frame: 6 hours
6 hours

Secondary Outcome Measures

Outcome Measure
Time Frame
Maximum ticagrelor and AR-C124900XX concentration at 6h after administration (Cmax6)
Time Frame: 6 hours
6 hours
Area under the plasma concentration-time curve for ticagrelor (AUC 0-6h)
Time Frame: prior to the initial dose and 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h post dose
prior to the initial dose and 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h post dose
Area under the plasma concentration-time curve for AR-C124900XX (AUC 0-6h)
Time Frame: prior to the initial dose and 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h post dose
prior to the initial dose and 15 min, 30 min, 45 min, 1h, 2h, 3h, 4h, 6h post dose
Platelet arbitrary aggregation units/min assessed by Multiple Electrode Aggregometry
Time Frame: prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose
prior to the initial dose and 30min, 1h, 2h, 3h, 4h, 6h post dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collegium Medicum w Bydgoszczy

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2016

Primary Completion (Actual)

December 1, 2017

Study Completion (Actual)

December 1, 2017

Study Registration Dates

First Submitted

October 18, 2016

First Submitted That Met QC Criteria

October 18, 2016

First Posted (Estimate)

October 19, 2016

Study Record Updates

Last Update Posted (Actual)

April 1, 2019

Last Update Submitted That Met QC Criteria

March 28, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CMUMK202F

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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